Protective function of taurine in glutamate-induced apoptosis in cultured neurons.
Previously, we showed that taurine protects neurons against glutamate-induced excitotoxicity by inhibiting the glutamate-induced increase of [Ca2+](i). In this study, we report that taurine prevents glutamate-induced chromosomal condensation, indicating that taurine inhibits glutamate-induced apoptosis. We found that Bcl-2 was down-regulated while Bax was up-regulated by glutamate treatment, and these changes were prevented in the presence of taurine. We have also shown that taurine inhibits glutamate-induced activation of calpain. Furthermore, calpastatin, a specific calpain inhibitor, also prevented glutamate-induced cell death. Here we propose the mechanisms underlying glutamate-induced apoptosis and taurine's inhibition of glutamate-induced apoptosis to be as follows: glutamate stimulation induces [Ca2+](i) elevation, which in turn activates calpain; activation of calpain leads to a reduction of Bcl-2:Bax ratios; with decreased Bcl-2:Bax ratios Bax homodimers form, Bax homodimerization, and translocation to the mitochondria result in the release of cytochrome c; released cytochrome c in turn activates a downstream caspase cascade leading to apoptosis. The antiapoptotic function of taurine is due to its inhibition of glutamate-induced membrane depolarization.
Leon
Rebecca
R
Department of Biomedical Science, Florida Atlantic University, Boca Raton, Florida 33431, USA.
Wu
Heng
H
Jin
Ying
Y
Wei
Jianning
J
Buddhala
Chandana
C
Prentice
Howard
H
Wu
Jang-Yen
JY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D013654:Taurine; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; D002154:Calpain; C506435:Casp9 protein, rat; D053453:Caspase 9; D002118:Calcium